A synthesis of cytochalasin D analogs is the long term goal of this project. During the coming year, the emphasis will be on preparation of the bicyclic lactam AB rings common to all of the cytochalasins. Several approaches based on Diels-Alder synthesis of the 6-membered B ring will be pursued. Upon completion of the AB ring system, methods for macrocycle synthesis based on 2, 3-sigmatropic ring expansion will be applied to introduce the C ring. Also, model studies for construction of the 11-membered ring of cytochalasin D will be carried out. Approaches using nitrogen or sulfur containing precursors are under study. Routes based on attachment of the AB rings to a preformed C ring will also be considered.